Prognostic implications of genotype findings in non‐ischaemic dilated cardiomyopathy: A network meta‐analysis

Abstract

AbstractAimsEvidence on the relative impact of diverse genetic backgrounds associated with non‐ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long‐term outcomes of different gene groups in DCM.Methods and resultsElectronic databases were systematically screened to identify studies reporting prognostic data on pre‐specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta‐analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67–2.65), MVAEs (OR 1.86, 95% CI 1.52–2.26), and HFEs (OR 2.01, 95% CI 1.08–3.73) than genotype‐negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20–2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non‐LMNA and non‐desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv.ConclusionsDifferent genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.